Abnormal neuronal excitation via agonist-receptor interactions may mediate long- term behavioral deficits following mild and moderate levels of traumatic brain injury (TBI). Brain information flow pathways may be disturbed by this abnormal excitation resulting in long-term changes in cell function that have measurable behavioral effects. We hypothesize that TBI may also produce widespread release of certain endogenous opioid peptides (and possibly other inhibitory neurotransmitters) that may act as endogenous protective substances. While the net effect of receptor-agonist interac- following TBI appears to be excitatory, opioids may provide some degree e of protection by acting as inhibitory modulators of CNS excitability at the receptor level. Application of appropriate exogenous ligand, d which mimic the protective actions of endogenous ligand, may provide additional protection. Behavioral experiments have demonstrated that TBI in the rat produces long-term motor and memory deficits. Preliminary data have shown that low doses of naloxone that preferentially bind to mu receptors tors (antagonist) exacerbate and morphine (mu agonist) reduces long-term behavioral deficits associated with TBI. Proposed research would include scintillation and autoradiographic studies of mu delta and kappa receptor binding in the rat brain. We will examine the effects of specific receptor subtype agonists and antagonists on long-term behavioral deficits (including memory), receptor binding and autoradiographic studies of regional cerebral blood flow.